| 1. |
- Klaff, Rami, 1971-
(författare)
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Disease-Specific Survival in Prostate Cancer Patients : Results from the Scandinavian Prostate Cancer Group (SPCG) Trial No. 5 and Regional Cancer Register Data
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- IntroductionProstate cancer (PCa) is the most common cancer among men in Sweden. The clinical course varies considerably, which makes it difficult to predict the prognosis in the individual case. In order to explore the early as well as the late course of the disease, large study groups and population-based cohorts are necessary.AimsTo explore factors that influence the long-term outcome of men with low-risk tumours in a population-based register, to predict the long-term course, and to assess the mortality rate for men with prostate cancer (Paper I)To analyse long-term outcome and to investigate factors associated with long-term survival in patients with metastases to the skeleton (Paper II)To analyse early androgen deprivation treatment (ADT) failure and to define clinical predictors associated with short survival due to early ADT failure in prostate cancer patients with bone metastases (Paper III)To analyse the prognostic significance of the extent of bone metastases in relation to other pretreatment variables in prostate cancer patients, and to explore the impact of bone metastases on quality-of-life (Paper IV)Material and methodsThe study groups were assembled from The South East Region Prostate Cancer Register (SERPCR), and The Scandinavian Prostate Cancer Group (SPCG) Trial No. 5. In the first study, prognostic factors and long-term disease-specific mortality rates of low-risk prostate cancer patients from the early PSA era were analysed. In the second study, patient-related factors, quality-of-life (QoL) and long-term survival in 915 PCa patients with bone metastases (M1b) under ADT, were analysed. In Study III factors predicting primary failure to respond to ADT were identified. Study IV explored the impact of the extent of bone metastases on survival and QoL for these men.Result and conclusionsThe long-term disease-specific mortality of low-risk localised PCa is low, but the annual mortality rate gradually increases. This indicates that some tumours slowly develop into lethal cancer, particularly in men 70 years or older and with a PSA level ≥ 4 μg/L. From the SPCG Trial No. 5, a subgroup of patients with M1b disease and favourable set of predictive factors survived more than 10 years under ADT with an acceptable QoL. Independent predictors of long-term survival were identified as performance status (PS) < 2, limited extent of bone metastases, and a PSA level < 231 μg/L at the time of enrolment in the trial. However, four independent clinical predictors of early ADT failure could be defined. Men exhibiting these features should be considered for an alternative treatment. Patient grouping based on three categories of extent of bone metastases related to PS, haemoglobin, and QoL at presentation, as independent predictors of mortality, may provide improved accuracy of prognosis.
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| 2. |
- Pettersson, Ulrika, 1970-
(författare)
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Bone mass in the young athlete
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bone mass and bone size accumulate during childhood and adolescence and peak in the twenties. The obtained peak bone mass has been suggested to be a major determinant of bone mass even in the very elderly. Although, genetic factors are the main determinants, environmental and lifestyle factors also play a crucial role in modulating maximal bone mass. Assessing these lifestyle factors would be of great importance for the intervention strategies against osteoporosis. The first aim of this thesis was to compare the bone mass and bone size in male and female young adults on a high level of physical activity with males or females on a low level of physical activity. Furthermore, it also aimed to investigate the influence of pubertal maturity, menstrual disturbances, and different body constitutional factors on bone mass and size during adolescence and young adulthood. The female activity groups consisted of cross-county skiers, soccer players, and rope skippers. Compared to their age-matched inactive controls, all these athletic groups demonstrated a significantly higher bone mineral density (BMD) at those sites subjected to the sport-specific loading. Rope-skipping, a very high impact activity was associated with a higher bone size, preferentially in the lower extremity, suggesting an effect of weight-bearing activity also on bone geometry. The effect of menstrual disturbances was evaluated in a group of long-distance runners, where amenorrheic runners had significantly lower BMD in both trabecular and also cortical bone in the lower extremity compared to eumenorrheic runners, suggesting that weight-bearing activity cannot compensate for the shortfall of reduced estrogen levels. The male activity groups consisted of ice hockey players and badminton players. Compared to their age-matched controls, both athletic groups demonstrated a significantly higher BMD at those sites subjected to the sport-specific loading. Especially badminton was associated with a high BMD, suggesting that physical activity, including jumps in unusual directions has a great osteogenic potential. The main determinants of BMD in both male and females were, except for type of physical activity, activity, muscle strength, height, and different body constitutional factors. However, the relationships with muscle strength and body constitution were somewhat weaker in the athletic groups, especially in the males, indicating that impact forces may be of greater importance in regulating bone mass in highly trained athletes. Yet bone size was largely determined by parameters related to body size and less strongly to physical activity. In a prospective study on adolescent boys, the changes in bone mass during late puberty were mainly accounted for by growth and development, including height and pubertal maturation, and less to physical activity level. Thus, the osteogenic effect from physical activity seems to be of importance for bone mass achievement predominantly before late puberty.
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| 3. |
- Marques, Catarina, 1969-
(författare)
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Studies on Cervical Artificial Disc Replacement
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Artificial disc replacement (ADR) was developed as an alternative to anterior fusion after decompression for cervical degenerative radiculopathy. By preserving motion, it was expected to prevent acceleration of adjacent segment pathology (ASP) associated with fusion, and lead to better clinical outcomes. The aims of this thesis were to evaluate whether ADR surgery leads to better outcomes than fusion surgery, to investigate if it prevents the acceleration of ASP, and to analyze its potential complications. In a multicenter randomized controlled trial (RCT) 153 patients were randomized to ADR (DiscoverTM implant) or fusion surgery (autograft, plate and screws). The outcomes at 5 and 10 years postoperatively were analyzed with Neck Disability Index (NDI) as primary measure. Heterotopic ossification (HO), ASP, and secondary surgery where analyzed. The measurements of radiographic parameters used in the assessment of cervical alignment where validated.To further analyze secondary surgery after ADR, a descriptive register cohort study was done with 42 patients whose data were retrieved from Swespine and completed with medical charts, images, and a telephone interview. There was no difference in NDI scores between groups in the RCT, 5 or 10 years postoperatively. Radiological and clinically significant ASP were similar in both groups. There was more secondary surgery in the ADR group compared with the fusion group, mainly due to device loosening in women. Severe HO was seen in 71% of the ADR implants 5 years postoperatively, and 27% were fused, male sex being a clear risk factor.Normative data for measurement error were provided on the cervical alignment measurements, and the most reliable were the K-line tilt and the cervical sagittal vertical axis (cSVA). In the 42 patients in the register cohort study the most common diagnosis leading to reoperation was loosening of the ADR implant and/or ASP, predominantly treated with fusion surgery. Reoperation resulted in good outcomes in the vast majority of patients. At the long-term, there is no clinical benefit of ADR over fusion surgery after decompression for cervical degenerative radiculopathy. ADR, compared with fusion surgery, does not prevent acceleration of ASP, and results in more reoperations. Revision surgery for failed cervical ADRs is effective and justified.
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| 4. |
- Malmgren, Linnea
(författare)
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Kidney Function During Ageing and its Association with Bone Mass, Fracture and Mortality
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Osteoporosis and osteoporosis related fractures are a major health care challenge both in Sweden and globally. The cost and suffering from osteoporosis are expected to increase since the population of elderly is increasing. Bone health can be affected by altered mineral homeostasis, which in its turn can be affected by reduced kidney function. However, the course of age-related decline in kidney function and its association to osteoporosis andfracture in the very elderly need further investigation since longitudinal data are scarce. Therefore, this thesis has two main aims; 1) to investigate kidney function during ageing and 2) its association to bone health in a cohort ofelderly women.Data was collected through the Malmö Osteoporosis Prospective Risk Assessment (OPRA) cohort, a prospective cohort of 1044 community dwelling women, all aged 75 and followed for ten years with reinvestigations at age 80and 85. Data on BMD, fracture and blood biochemistry was available at all three time points.Estimated kidney function greatly depends on which marker and study equation is used. The discrepancies are to such an extent that could affect whether a person is diagnosed with chronic kidney disease (CKD) or not, of particular importance in the elderly. Only women with the worst kidney function, corresponding to CKD stage 3b-5, had continuously increased mortality risk. This indicates that an age-dependent CKD definition would be of valuein elderly women.Kidney function in elderly women was associated with markers of mineral homeostasis, bone loss and BMD, but the effect size was relatively small compared to other risk factors. Also, fracture risk was increased only in womenwith mild-moderate reduction of kidney function (CKD stage 3a) and not in women with the worst kidney function (CKD stage 3b-5). Low BMD was associated with increased fracture risk independent of kidney function. Havingboth reduced kidney function and osteoporosis could present an additional risk increase.In conclusion, estimated kidney function in elderly women greatly depends on method of estimation and the results advocate for an age-adapted CKD definition. Maintaining adequate kidney function is important formaintaining bone health, although in old age it is probable that the effect size of any single specific risk factor is smaller compared with younger individuals.
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| 5. |
- Sandberg, Olof, 1985-
(författare)
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Metaphyseal Fracture Healing
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Most of what is known about fracture healing comes from studies of shaft fractures in long bones. In contrast, patients more often have fractures closer to the ends (metaphyses). Here most bone tissue has a spongy, cancellous structure different from the compact bone of the shaft. There is an increasing awareness that metaphyseal fractures heal differently. However, the more easily studied shaft healing has usually been considered as good enough representative for fracture healing in general.My work shows that the biology of metaphyseal healing is more different from shaft healing than was previously known and that this has implications on the effect of various commonly prescribed drugs.First we studied biopsies of healing cancellous bone collected from human donors. We found that the most abundant new bone formation occurred freely in the marrow rather than on the surface of old trabeculae, as described in most literature. There was little cartilage, indicating that the dominant bone formation process is mostly membranous in nature. This is a contrast to the ample cartilage formation commonly found in the well-characterized shaft fracture models.Next we characterized a model that allows for mechanical quantification of regenerating cancellous bone. By contrasting this cancellous healing model with the standard shaft healing model we could demonstrate that the NSAID indomethacin, the glucocorticoid dexamethasone, and the bisphosphonate alendronate all had different effects on the mechanical quality of bone regeneration in shaft and metaphysis; while anti-inflammatory drugs strongly impaired shaft healing, metaphyseal healing was not similarly affected. Alendronate had a positive effect on both models, though the effect was strongest in the metaphyseal model. Taken together these differences shed some light as to the differences in healing biology.The last step (within the boundaries of this thesis) was a characterization of how healing in cortical and cancellous bone differs in terms of immune cell involvement. We could find little difference between the two bone types day 3. However, day 5 an increase in the number of granulocytes could be noted in the cancellous bone while the cortical bone had a higher number of lymphocytes.To conclude, this work furthers our understanding of how metaphyseal healing differs from shaft healing. It has clinical implications as it motivates an increased attention to the site of fracture while contemplating treatment. I hope this thesis can be read as an argument for increased interest in metaphyseal fracture healing.
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| 6. |
- Ericsson, Ylva
(författare)
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Knee function, Physical Activity and Perceived Health after Meniscectomy in the Middle-aged
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to explore the impact of meniscal injury and meniscectomy on joint and muscle function, physical activity and perceived health in middle-age subjects and to evaluate the effect of a functional exercise program. Male and female post meniscectomy patients participated in Studies I-IV (n=45 in Studies I-III, n=99 in Study IV) and Study IV also included 94 controls. Outcome measures were thigh muscle strength, functional performance tests, femoral cartilage quality (assessed by dGEMRIC) and Body Mass Index (BMI) in addition to four questionnaires: the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Knee Self Efficacy Scale (K-SESABC), the Physical Activity Scale (PAS) and the MOS Short Form-36 (SF-36) health scale. Studies I-II revealed that patients had less strength in the operated compared to the nonoperated leg (mean difference 9%) and the deficit was associated with symptoms and functional limitations (KOOS). Cartilage quality (dGEMRIC Index) in the medial compartment was 14% lower than in the lateral, and correlated positively with thigh muscle strength/BW and negatively with BMI. In study III, patients were randomized to a four- month functional exercise intervention or to no intervention. The exercise group tolerated the training well and improved in one-leg hop, hamstrings strength and quadriceps endurance. In study IV patients scored lower than controls in K-SES and in two SF-36 subscales. Only 46% of the patients had resumed their pre-injury PA level, although current PA did not differ between the groups. In the patient group, K-SES was associated with PAS (rs=0.42) and SF-36 (rs= 0.35-0.85). Female patients scored lower than male patients in K-SES and four SF-36 subscales. In conclusion, patients were found to have considerable symptoms, functional limitations and lower self efficacy than controls 3-4 years after meniscectomy. Strong thigh muscles seem to be helpful for improving knee function and protecting knee cartilage, whereas high BMI appears to be harmful to the cartilage. Functional exercise training after meniscectomy could be a useful method for restoring knee function, thus helping patients to resume PA and maintain good health.
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| 7. |
- Leonardsson, Olof
(författare)
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Arthroplasty for Femoral Neck Fracture. Results of a nationwide implementation.
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hip fractures are devastating for the individual and a substantial economic burden for society. The treatment for displaced femoral neck fracture is a choice between internal fixation, total hip arthroplasty and hemiarthroplasty. As a result of several randomized trials, the treatment has shifted in Sweden from mostly internal fixation towards arthroplasties. There have been concerns about long-term arthroplasty complications such as aseptic loosening and periprosthetic fracture. In addition to investigating this issue, the focus of this thesis was on identifying the optimal treatment methods for patients with this displaced femoral neck fractures, regarding choice of implant and surgical technique. In a 10-year follow-up of a randomized multicenter trial on 450 mentally lucid and relatively healthy patients above 70 years with displaced femoral neck fractures, patients treated with internal fixation had continuously higher rates of major complications compared to those treated with arthroplasty (46 % compared to 9 % at 10 years). Patients with successful healed fractures reported more pain and reduction of mobility at four months than those successfully treated with arthroplasty, and they never attained a better result than the latter. Those results indicate that there are no excess long-term complications after arthroplasty and refute the assumption that retaining the patient’s femoral head is beneficial. The Swedish Hip Arthroplasty Register records total hip arthroplasties since 1979 and hemiarthroplasties since 2005. All hospitals performing arthroplasty surgery in Sweden are participating and completeness of recordings is near 100 %. In a study based on data from the Swedish Hip Arthroplasty Register, patients with fracture-related total hip arthroplasty had a higher revision rate than those treated for other reasons (mainly osteoarthritis); 4.4 % compared to 2.9 % at 7 years. Revision rates were similar after acute fracture procedures and procedures performed secondary to failed internal fixation. Contrasting, hemiarthroplasties in the Swedish Hip Arthroplasty Register performed secondary to failed internal fixation were associated with a doubled risk of re-operation compared to those performed for acute fracture. Anterolateral surgical approach had a lower risk of total hip arthroplasty revision regardless of reason and hemiarthroplasty re-operation due to dislocation. Bipolar and uncemented hemiarthroplasties were risk factors for re-operation; the former due to dislocation, infection and periprosthetic fracture, the latter mainly due to periprosthetic fracture. Males had higher risk of total hip arthroplasty revision and hemiarthroplasty re-operation as well as higher risk of death within one year following the injury. Nationwide, the proportion of hemiarthroplasty procedures for acute fractures increased from 2005 through 2009 at the expense of those secondary to failed internal fixation. Use of monoblock type implants decreased to below 1 %. Modular implants increased generally, while in 2009 bipolar implants decreased in favor of unipolar. Uncemented implants and posterior surgical approach decreased. Assumedly, those changes are results of reports from clinical trials and the Swedish Hip Arthroplasty Register. In collaboration between the Swedish Hip Arthroplasty Register and the National Hip Fracture Register, all Swedish patients with displaced femoral neck fractures during 2009 received a mailed patient-reported outcomes questionnaire (79 % response rate). Patients above 70 years, with total hip arthroplasty reported less pain and were more satisfied than those treated with internal fixation or hemiarthroplasty at a median of 14 months after the fracture. Among patients below 70, those treated with total hip arthroplasty had less pain and were more satisfied than those with internal fixation. The results presented in this thesis support the use of arthroplasty as primary treatment for displaced femoral neck fractures and indicate that use of total hip arthroplasties could be increased even further. The higher risk of re-operation with bipolar implants implies that unipolar hemiarthroplasty may be preferable for the oldest. Finally, the results suggests that anterolateral surgical approach and cemented implants are preferable in fracture-related arthroplasty surgery.
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| 8. |
- Nyström, Andreas, 1972-
(författare)
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Uncemented Total Hip Arthroplasty : Aspects on Bone Biology, Implant Fixation, Periprosthetic Bone Remodeling, Bone Mineral Density and Effects of Denosumab
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Uncemented total hip arthroplasty (THA) is associated with loss of periprosthetic bone mineral density (BMD). The collum femoris preserving (CFP) stem lost 28% of proximal BMD at 2 years. The overall purpose of this thesis was to study the long-term results of the CFP stem in BMD and implant stability (study III) and whether periprosthetic BMD can be preserved with denosumab (study I). Secondary objectives were to evaluate a CT-based technique as an alternative to radiostereometric analysis (RSA) and investigate the reliability, agreement, and precision of periprosthetic [18F]-fluoride PET/CT (F-PET). In study I, a randomized controlled trial, we studied the effect of denosumab on 1) periprosthetic BMD by dual-energy x-ray absorptiometry (DXA), 2) periprosthetic bone formation by F-PET, and 3) serum markers of bone turnover. We found that denosumab prevents early periprosthetic bone loss and reduces periprosthetic and systemic bone turnover. Study II is a methodologic-, multicenter study investigating the precision of low-dose CT-based implant motion analysis (CTMA). We determined the precision of CTMA by repeated measures and found it to be high. In study III we examined the long-term results of the CFP stem. The cohort from a previous, prospective study on the CFP stem was followed up for a minimum of 8 years with DXA and RSA. Periprosthetic BMD was not restored, and further bone loss was seen in the proximal part of the femur; however, the stems appeared stable on RSA. In study IV, we looked at the reliability, agreement, and precision of periprosthetic F-PET. F-PET investigations from study I were analyzed twice by two independent observers, at least 3 weeks apart. Reliability was excellent, agreement was high, and precision was moderate between and within observers. In conclusion, denosumab prevents periprosthetic BMD loss and the CFP stem shows continuous periprosthetic bone loss 8 years after surgery, but the implants remain stable. In addition, this thesis shows that CTMA is a precise method and a viable alternative to RSA. Finally, it demonstrates that periprosthetic F-PET is a reliable method with high inter- and intraobserver agreement.
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| 9. |
- Rosengren, Björn
(författare)
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Hip Fracture Incidence and Prevalence of Osteoporosis in Sweden in Recent Decades
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An increase in hip fracture incidence during the recent half-century has been reported worldwide and has been predicted to continue. Recent publications, however, have reported stable or even decreasing hip fracture incidence. No reports evaluate whether these changes in hip fracture incidence are associated with changes in bone mineral density (BMD), if they apply in both urban and rural settings, and few have tried to analyze whether they are attributable to cohort and/or period effects. In population-based samples of urban and rural women (n=437, age ≥50 years) and men (n=277, age ≥60 years) risk factors for hip fracture were evaluated in 1988/89 and 1998/99 as was BMD in Malmö women from 1970 to 1999 (n=459, age ≥50 years). The annual number of hip fractures in the respective region, gender and age group as well as nationwide in all individuals aged ≥50 years were obtained from central national inpatient data from 1987 to 2002 and in Malmö women from 1967 to 2001 by local records. Age-Period-Cohort (APC) effects were evaluated by log likelihood estimates in Poisson regression models. In all local cohorts the age-standardized hip fracture incidence was stable from 1987 to 2002 and from 1969 to 2001, and BMD and prevalence of osteoporosis were stable between 1974 and 1999 and between 1988/89 and 1998/99. In nationwide Swedish data hip fracture incidence was stable from 1987 to 1996, after which a decrease was evident. There were evident period+cohort effects in women, with a major reduction in hip fracture incidence by subsequent birth cohorts (estimated incidence rate ratio 2.2 comparing women born 1889–96 to women born 1945–52). This thesis infers that the hip fracture incidence has levelled off also in Sweden and has since the mid 1990s been replaced by a decreasing annual incidence. In women this appear to be the result of cohort+period effects, in that that those born more recently had a lower incidence than those born earlier. As no differences in BMD or prevalence of osteoporosis were apparent, the changes in hip fracture incidence seem attributable to other factors, probably linked to the major changes in society during the century-long lifespan of the examined individuals. The data presented in this thesis are important both for projecting future hip fracture burden and when planning for hip fracture resources in the future.
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| 10. |
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